We are investigating the molecular events leading to the establishment of herpes simplex virus latent infections in the nervous systems of experimentally infected mice and of humans, and are determining the possible role of herpes simplex virus in neoplastic transformation. Regions of homology between the HSV genome and those of mice and humans have been identified and the viral and cellular DNA sequences are being determined. A portion of the viral homologous sequences has been found within the regulatory region of the T24 human oncogene derived from a bladder carcinoma. HSV specific DNA sequences have been detected by in situ hybridization, in the nucleus caudalis of the trigeminal complex of the brain stem and in the midline reticular formation and trigeminal motor nucleus of the brain hemispheres in latently infected mice. The gene coding for one of the major determinants on the virus surface of HSV-1 has been mapped and their cloning in bacterial expression plasmids is in progress.